Human Immunodeficiency Virus 1 (HIV-1) remains one of the leading causes of death worldwide predominantly in resource-limited countries. The present Combined Antiretroviral Therapy (cART) has significantly reduced disease mortality among patients. However, the virus still persists in viral reservoir organs such as Gut-associated lymphoid tissue (GALT). Mostly cART drugs have failed to eradicate GALT reservoir because of its complex physiology. In this regard, drugs that specifically reach out to that remote lymphatic tissue at therapeutic level for an extended period of time will be of current interest. Considering the next-generation therapy for HIV-1 as one of the priority research areas of Office of AIDS Research, we propose to develop a nanomedicine based long-acting anti-HIV drug formulation targeting Microfold cells (M-cell) in the GALT. M-cells are specialized epithelial cells that are predominantly present in the gastrointestinal tract. It effectively transports many micromolecules to the underlying mucosal immune system. Considering the transcytosis property of M-cell, we have developed a pluronic nanocarrier containing three currently recommended anti-HIV drugs (also called nanodrug). This nanodrug is bio-conjugated with anti-M-cell specific antibody for targeted drug delivery to M-cell. We hypothesize that an M- cell mediated drug delivery will be more sustained and effective than conventional drugs to the GALT.